Breast cancer is among the most commonly diagnosed cancers, and it causes the second highest female mortality rate in the United States. (Parker S et al., Cancer Statistics, 1997, CA Cancer J Clin 1997, 47:5-27; Jemal, A. et al., Cancer Statistics, 2004, CA Cancer J Clin 2004, 54:8-29). Early and accurate diagnosis of breast cancer is critical to successful intervention.
Scintimammography is an adjunct diagnostic tool for patients with suspected breast cancers. (Khalkhali I et al., 99mTc Sestamibi Breast Imaging for the Examination of Patients with Dense and Fatty Breasts: Multicenter Study, Radiology 2002, 222:149-155; Khalkhali I et al., Scintimammography: The Complementary Role of Tc-99m Sestamibi Prone Breast Imaging for the Diagnosis of Breast Carcinoma, Radiology 1995, 196:421-426; Hussain R et al., A meta-analysis of scintimammography: an evidence-based approach to its clinical utility, Nu Med Comm 2006, 27:589-594). The technique provides physiological information about the target tissue by utilizing mitochondria-targeting tracers. (Hussain R et al., 2006; Mathieu I et al., Inconclusive Triple Diagnosis in Breast Cancer Imaging: Is There a Place for Scintimammography?, J Nucl Med 2005, 46:1574-1581; Liberman M et al., Breast cancer diagnosis by scintimammography: a meta-analysis and review of the literature, Breast Canc Res Treat 2003, 80:115-126).
Imaging agents that have been used in scintimammography include 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) and 99mTc-tetrofosmin. (Sampalis F et al., International prospective evaluation of scintimammography with 99mTechnetium sestamibi, The Am J of Surg 2003, 185:544-549; Spanu A et al., 99mTc-tetrofosmin SPET in the detection of both primary breast cancer and auxiliary lymph node metastasis, European J of Nucl Med 2001, 28(12):1781-1794). Although originally developed as heart imaging agents, the elevated uptake of these mitochondria-targeting agents in carcinomas positively correlates to cancer invasiveness. Elevated uptake is also attributable to active angiogenesis and aberrant oxidative metabolism of tumor cells. (Delmon-Moingeon L et al., Uptake of the Cation Hexakis(2-methoxyisobutylisonitrile)-Technetium-99m by Human Carcinoma Cell Lines in Vitro, Canc Res 1990, 50:2198-2202; Papantoniou V et al., The Potential Role of Calcitonin Gene-Related Peptide (CGRP) in Breast Carcinogenesis and Its Correlation With 99mTc-(V)DMSA Scintimammography, Am J of Clinical Oncology 2007, 30(4)420-427). However, cardiac and hepatic uptake of the existing agents is relatively high in breast imaging, which tends to cause background noise due to close proximity of the heart and liver to mammary tissues.